Studies will be directed towards establishing the structural basis of inherited differences in the functional capacity of three proteins critical to nerve function: monoamine oxidase (MAO), catechol-O-methyltransferase (COMT) and the Beta subunit of nerve growth factor (Beta-NGF). Proteins will be analyzed from human peripheral tissues: placenta, platelets, lymphocytes and cultured skin fibroblasts for MAO, erythrocytes and fibroblasts for COMT, and fibroblasts for Beta-NGF. Each protein will be compared in the same tissue from different donors and from different tissues of the same donor. Donors will include individuals in whom atypical function of these proteins has been documented, including patients with familial dysautonomia and schizophrenia, as well as their family members. Proteins will be characterized by gel electrophoresis on the basis of MW and charge in the presence of sodium dodecyl sulfate and under conditions of isoelectric focusing, respectively. The position of specific proteins on gels will be identified by immunofixation techniques with 125-protein A as a "second antibody". Antigenic differences among proteins will be resolved using monoclonal antibodies. Fine structural analysis will be carried out by peptide mapping. Small amounts of specific proteins will be purified by immunoprecipitation and gel electrophoresis, then iodinated and exposed to site-specific cleavage agents. Peptide fragments will be resolved on the basis of amino acid composition by high pressure liquid chromatography. The objective is to determine whether inherited variations in the structure of these proteins underlie individiual differences in neurophysiology, drug metabolism and susceptibility to neurologic and psychiatric disease.